Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Germ Cell Tumors

Basic Trial Information

Objectives

1. Determine the safety of paclitaxel and ifosfamide followed by carboplatin and etoposide with stem cell support in patients with unfavorable germ cell tumors with unfavorable prognostic factors and resistance to cisplatin.
2. Determine the efficacy of this regimen as salvage therapy in these patients.
3. Escalate the dose of carboplatin based on a target area under the concentration time curve and renal function, and determine the pharmacokinetics of carboplatin in selected patients.
4. Determine the qualitative effects of paclitaxel and ifosfamide on hematopoietic progenitors in these patients.

Entry Criteria

Disease Characteristics:

• Histologically proven advanced germ cell tumor that is resistant to a cisplatin-based chemotherapy regimen
• Must meet 1 of the following conditions:
  • Measurable or evaluable disease
  • Elevated serum tumor markers (alpha-fetoprotein or human chorionic gonadotropin)
  • Known residual disease after postchemotherapy surgery
• Unfavorable prognostic factors for achieving a complete response to cisplatin-based salvage therapy required, including either:
  • Extragonadal primary site

    OR

  • Testis/ovarian primary with incomplete response to first-line therapy
• No marrow involvement with tumor on pretherapy bone marrow aspiration and biopsy
  • Marrow must be normocellular

Prior/Concurrent Therapy:

Biologic therapy:

• No prior autologous bone marrow transplantation with high-dose therapy

Chemotherapy:

• See Disease Characteristics
• No more than 5 prior courses (4 preferred) of cisplatin
• At least 3 weeks since prior chemotherapy
• No other concurrent chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• See Disease Characteristics
• Recovered from recent surgery

Patient Characteristics:

Age:

• 14 and over

Performance status:

• Not specified

Hematopoietic:

• WBC at least 3,000/mm3
• Platelet count at least 100,000/mm3

Hepatic:

• Not specified

Renal:

• Creatinine clearance greater than 50 mL/min
• Renal dysfunction due to ureteral obstruction by tumor allowed at the discretion of the principal investigator

Cardiovascular:

• If history of significant cardiac disease, evaluation and clearance by a cardiologist required before study entry

Other:

• HIV negative
• No active infection
• General medical condition sufficient to allow general anesthesia at the time of marrow harvest

Expected Enrollment

A total of 10-30 patients will be accrued for this study within 1-2 years.

Outline

This is a dose escalation study of carboplatin.

Patients are treated on regimen A followed by regimen B.

• Regimen A: Patients receive paclitaxel IV continuously on day 1 and ifosfamide IV over 4 hours on days 2-4. Autologous peripheral blood stem cells (PBSC) are harvested on days 11-13. Filgrastim (G-CSF) is administered subcutaneously (SC) twice daily beginning 6 hours after completion of paclitaxel and ifosfamide infusions and continuing until the last day of leukapheresis. Treatment continues every 2 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Before beginning the first course of chemotherapy, autologous bone marrow (ABM) is harvested, if possible, in case insufficient peripheral blood stem cells (PBSC) are harvested. Patients who were unable to undergo harvest of ABM before the first course of chemotherapy undergo harvest of ABM before beginning the second course of chemotherapy.
• Regimen B: Beginning 2 weeks after completion of regimen A, patients receive etoposide IV over 2 hours and carboplatin IV over 1 hour on days 1-3. PBSC are reinfused on day 5. G-CSF is administered SC twice daily beginning 6 hours after completion of etoposide and carboplatin infusions and continuing until blood counts recover. G-CSF is held on the morning of PBSC transplantation and restarted beginning 6 hours after completion of PBSC transplantation. Treatment continues every 2 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients with insufficient PBSC for the second course receive PBSC combined with ABM. Patients with insufficient PBSC for the third course receive ABM.

  During regimen B, cohorts of 3-6 patients receive escalating doses of carboplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 6 patients experience dose-limiting toxicity.

After completion of regimens A and B, some patients may undergo resection of residual masses.

Feldman DR, Sheinfeld J, Bajorin DF, et al.: TI-CE high-dose chemotherapy for patients with previously treated germ cell tumors: results and prognostic factor analysis. J Clin Oncol 28 (10): 1706-13, 2010.[PUBMED Abstract]

Kondagunta GV, Bacik J, Sheinfeld J, et al.: Paclitaxel plus Ifosfamide followed by high-dose carboplatin plus etoposide in previously treated germ cell tumors. J Clin Oncol 25 (1): 85-90, 2007.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Gnanamba Kondagunta, MD, Protocol chair		Ph: 646-422-4306; 800-525-2225

Registry Information
Official Title		Phase I Trial of Sequential Taxol/Ifosfamide and Dose-Intensive Carboplatin/Etoposide With Stem Cell Support in Cisplatin-Resistant Germ Cell Tumor Patients With Unfavorable Prognostic Features
Trial Start Date		1994-01-25
Trial Completion Date		2009-04-28
Registered in ClinicalTrials.gov		NCT00002558
Date Submitted to PDQ		1994-01-25
Information Last Verified		2007-03-08
NCI Grant/Contract Number		CA08748

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